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Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium.

Bromage, DI; Davidson, SM; Yellon, DM; (2014) Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium. Pharmacol Ther , 143 (3) 305 - 315. 10.1016/j.pharmthera.2014.03.009. Green open access

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Abstract

Alleviating myocardial injury associated with ST elevation myocardial infarction is central to improving the global burden of coronary heart disease. The chemokine stromal cell-derived factor 1α (SDF-1α) has dual potential benefit in this regard. Firstly, SDF-1α is up-regulated in experimental and clinical studies of acute myocardial infarction (AMI) and regulates stem cell migration to sites of injury. SDF-1α delivery to the myocardium after AMI is associated with improved stem cell homing, angiogenesis, and left ventricular function in animal models, and improvements in heart failure and quality of life in humans. Secondly, SDF-1α may have a role in remote ischaemic conditioning (RIC), the phenomenon whereby non-lethal ischaemia-reperfusion applied to an organ or tissue remote from the heart protects the myocardium from lethal ischaemia-reperfusion injury (IRI). SDF-1α is increased in the serum of rats subjected to RIC and protects against myocardial IRI in ex vivo studies. Despite these potential pleiotropic effects, a limitation of SDF-1α is its short plasma half-life due to cleavage by dipeptidyl peptidase-4 (DPP-4). However, DPP-4 inhibitors increase the half-life of SDF-1α by preventing its degradation and are also protective against lethal IRI. In summary, SDF-1 potentially delivers a 'two-pronged' defence of the myocardium: acutely protecting it from IRI while simultaneously stimulating repair by recruiting stem cells to the site of injury. In this article we examine the evidence for acute and chronic cardioprotective roles of SDF-1α and discuss potential therapeutic manipulations of this mechanism with DPP-4 inhibitors to protect against lethal tissue injury in the clinical setting.

Type: Article
Title: Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.pharmthera.2014.03.009
Publisher version: http://dx.doi.org/10.1016/j.pharmthera.2014.03.009
Language: English
Additional information: This article is available under the terms of the Creative Commons Attribution License (CC BY) as indicated via the Publisher Version link above.
Keywords: AMI, CXCR4, Cardioprotection, DPP-4, Ischemic conditioning, SDF
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/1427281
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